Healthy Volunteers in First in Human Oncology Drug Development for Small Molecules.

This review provides tools to consider the inclusion of healthy volunteers (HVs) in first in human (FIH) oncology clinical trials with small molecules, including targeted and immunomodulatory agents, a strategy that was not envisioned with classic chemotherapy. To enable a FIH oncology trial in HVs compared to cancer patients (CPs), a robust nonclinical package must be generated, which includes toxicokinetic and pharmacokinetic, more extensive safety pharmacology, toxicology and genotoxicity studies. This strategy could provide an early clinical characterization of the pharmacokinetic parameters and clinical safety profile in the absence of comorbidities and concomitant medication. It also avoids the ethical issue of administrating sub-therapeutic doses to CPs, and could potentially help to accelerate the timelines of clinical drug development for patient care. That being said, stakeholders involved in these studies need to proceed with caution, fully understand the regulatory guidance and thoroughly evaluate the benefits and risks. This paper serves to address the regulatory guidance and other considerations needed when using healthy volunteers in early oncology trials.